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Prostaglandin D 2 (PGD 2 ) released by degranulating mast cells is believed to play a key role in orchestrating mechanisms of inflammation in allergies and asthma. The biological effects of PGD 2 are mediated by D-prostanoid (DP1), CRTH2 (DP2), and thromboxane prostanoid (TP) receptors. The CRTH2 receptor is involved in induction of migration and activation of T helper type 2 (Th 2 ) lymphocytes, eosinophils, and basophils; up-regulation of adhesion molecules; and promotion of pro-inflammatory Th 2 -type cytokines (interleukin [IL]-4, 5, 13), whereas the DP receptor is associated with relaxation of smooth muscles, vasodilation, inhibition of cell migration, and apoptosis of eosinophils. A number of CRTH2/PGD 2 receptor antagonists have been investigated in asthma and allergic diseases. The CRTH2 antagonist (OC000459) or dual CRTH2 and TP receptor antagonist (ramatroban) were effective in reducing eosinophilia, nasal mucosal swelling, and clinical symptoms of allergic rhinitis, with the latter drug registered for clinical use in this indication. OC000459 and setipiprant reduced the late but not early phase of response in an allergen challenge in atopic asthmatics. In persistent asthma, some molecules induced limited improvement in lung function, quality of life, and asthma symptoms (OC000459, BI671800), but in other trials with AMG 853 and AZ1981 these findings were not confirmed. The clear discrepancy between animal studies and clinical efficacy of CRTH2 antagonism in allergic rhinitis, and lack of efficacy in a general cohort of asthmatics, highlight the issue of patient phenotyping. There is no doubt that the PGD 2 /CATH2/DP1 pathway plays a key role in allergic inflammation and further studies with selective or combined antagonisms in well defined cohorts of patients are needed.

Patients with moderate-to-severe asthma may now be treated using a variety of monoclonal antibodies that target key inflammatory cytokines involved in disease pathogenesis. Existing clinical data on anti-IgE, anti-IL-5 and other immunological pathways indicate these therapies to offer reduced exacerbation rates, improved lung function, greater asthma control and better quality of life. However, as several patients still do not achieve satisfactory clinical response with the antibodies available, many more biologics, aiming different immunological pathways, are under evaluation. This review summarizes recent data on existing and potential monoclonal antibodies in asthma. Recent advances have resulted in the registration of a new antibody targeting TSLP (tezepelumab), with others being under development. Some of the researched monoclonal antibodies (e.g. anti-IL-13 tralokinumab and lebrikizumab or anti-IL-17A secukinumab) have shown optimistic results in preliminary research; however, these have been discontinued in asthma clinical research. In addition, as available monoclonal antibody treatments have shown little benefit among patients with T 2 -low asthma, research continues in this area, with several antibodies in development. This article summarizes the available pre-clinical and clinical data on new and emerging drugs for treating severe asthma, discusses discontinued treatments and outlines future directions in this area.

Asthma is among the most common chronic respiratory diseases, affecting approximately 3340 individuals per 100,000 worldwide. It is a heterogeneous condition associated with airway hyperresponsiveness and chronic inflammation. Severe asthma (SA) affects 3–10% of patients, most of whom exhibit Type 2 (T2) inflammation with elevated eosinophil counts or increased fractional exhaled nitric oxide. Although the Global Initiative for Asthma provides detailed guidelines for SA, patients with marked hypereosinophilia (HE; >1500 cells/µL) who do not meet diagnostic criteria for hypereosinophilic syndrome (HES) or eosinophilic granulomatosis with polyangiitis (EGPA) remain insufficiently addressed. In such cases, oral corticosteroids, and T2-targeted monoclonal antibodies (MAbs) inhibiting interleukin-5 or its receptor are the main therapeutic options. For instance, mepolizumab is approved for EGPA, HES, and chronic rhinosinusitis with nasal polyps, but its use in hypereosinophilic SA is limited by eligibility, tolerance, or effectiveness. SA with HE not classified as HES or EGPA is exceptionally rare and may be diagnosed by the exclusion of other potential causes of HE. This review analyzes recent studies and case reports, aiming to expand the understanding of this underrecognized clinical entity, its relation to T2 inflammation and eosinophilic disorders, and to highlight the need for improved diagnostic and therapeutic strategies.

Patients’ collaboration with healthcare providers, along with their individual dedication to follow medical recommendations, is a crucial component of effective therapy in chronic diseases. If a patient fails to fill their prescription, administers the medication improperly in terms of method and/or dosage, misses follow-up visits, or discontinues the treatment for any reason, these lapses can adversely affect disease management, impairing the effectiveness of symptom relief and prevention of progression and complications. A comparable situation pertains to allergic diseases, which require long-term and consistent treatment to achieve symptom alleviation and control. Research has shown that adherence rates for long-term therapy in chronic diseases have improved marginally over the years and continue to hover at approximately the figure published in a World Health Organization (WHO) report “Adherence to long-term therapies: evidence for action.” from 2003, which had stated that only 50% of patients in developed countries follow medical recommendations and that this rate would be even lower in developing countries. Over 20 years later, literature indicated that there has been only a slight improvement on the matter, leaving room for developing and implementing effective solutions to improve medication compliance. Further investigation on this matter is required. Causes for non-adherence classified by the Global Initiative for Asthma in their main report seem to correspond to those of the report by the WHO. Similar dependency might be determined by other allergic diseases as they fit chronic disease criteria, and the issue of non-adherence affects them too. This literature review seeks to compile and synthesize current insights on factors that influence adherence, as well as explore potential methods for monitoring, evaluating, and improving its outcomes in chronic diseases related to the medical field of allergology, such as asthma, allergic rhinitis, allergic conjunctivitis, rhinoconjunctivitis, atopic dermatitis, and urticaria.

Introduction: Recent data indicate that approximately 10–20% of patients with severe asthma (SA) receiving benralizumab (BENRA) do not achieve the desired outcomes. Emerging evidence suggests that clinical remission (CRem) is possible with biologics, warranting investigations into predictive factors. Methods: In this retrospective, single-center study, we analyzed 103 SA patients treated with BENRA for 12 months. CRem was defined as meeting four criteria: no exacerbations requiring oral corticosteroids (OCSs), discontinuation of chronic OCS therapy, improvement in FEV1 ≥100 mL, and an ACQ score < 1.5. Logistic regression identified predictors of remission. Results: After 12 months, 33% of patients achieved CRem, while 10% discontinued treatment due to lack of improvement. BENRA reduced the annual exacerbation rate from a median of 2 to 0 (p < 0.0001) and eliminated OCS use in 80% of patients. Lung function improved significantly, with a +13.5% predicted increase in FEV1 (p < 0.0001). Asthma control also improved, with ACQ scores decreasing from 3.2 to 1.5 (p < 0.0001) and mini-AQLQ scores increasing from 3.4 to 5.0 (p < 0.0001). Key predictors of remission included baseline eosinophil count ≥740 × 103/μL (OR = 3.91, p = 0.02), SA duration (OR = 0.90, p = 0.02), baseline quality of life (OR = 2.18, p = 0.04), and pre-treatment FEV1 (OR = 1.07, p = 0.005). The logistic regression model for these parameters showed strong predictive accuracy (AUC = 0.855, 95% CI 0.78–0.93). Importantly, the SA phase, rather than total asthma duration, was the critical factor, with each additional year reducing the odds of remission by ~10%. Conclusion: Clinical remission is a realistic goal in severe asthma, and early initiation of biologic therapy is vital for improving remission rates and long-term outcomes.

Background: Treatment compliant with the Global Initiative for Asthma (GINA) can promote more effective disease control. Single-inhaler triple therapy (SITT) is one method that is used to optimize therapy in this context, but TRIPLE therapy is still employed by physicians to a limited extent. Objective: This study aimed to describe the factors influencing challenges in optimizing asthma therapy. Methods: A 19-question survey, created via the CATI system, was distributed among pulmonologists, allergologists, general practitioners, and internal medicine specialists in Poland, Greece, Sweden, Slovenia, and Austria. Results: Statistically significant percentage differences in the use of TRIPLE therapy in the context of asthma management were observed among countries as well as between pulmonologists, allergists, and other specialists. Overuse of oral corticosteroids (OCSs) to treat nonsevere and severe asthma in the absence of an approach that focuses on optimizing inhalation therapy among asthma patients receiving TRIPLE therapy was observed in different countries as well as among physicians with different specialties. Twenty elements associated with the challenges involved in diagnosing and managing difficult-to-treat and severe asthma were identified. Six clinical categories for the optimization of asthma therapy via SITT were highlighted. The degree of therapeutic underestimation observed among severe asthma patients was assessed by comparing actual treatment with the recommendations of the GINA 2023 guidelines. Conclusions: Physicians of various specialties in Europe are subject to therapeutic inertia in terms of their compliance with the GINA 2023 guidelines.

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Background: Idiopathic hypereosinophilic syndrome (iHES) is a rare disorder of persistent hypereosinophilia with secondary organ damage, but the full spectrum of organ involvement and the constitutional-symptom burden under systematic ascertainment remain incompletely characterised. Objectives: To describe the clinical phenotype of iHES in a large single-centre cohort, with attention to symptoms typically under-reported in observational series. Methods: We followed 72 consecutive patients with iHES at a tertiary referral centre between January 2017 and May 2025. Defined HES variants were excluded by FIP1L1-PDGFRA RT-PCR and aberrant T-cell phenotyping on flow cytometry; secondary causes were excluded clinically. Each potential organ manifestation was systematically assessed at every visit using a structured clinician-administered checklist. Wilson 95% confidence intervals (CIs) are reported for all proportions. Results: Median age at diagnosis was 45 years (interquartile range [IQR] 31–58); 83% were female. The median number of involved organ systems was 3 (IQR 2–4, range 1–6). Pulmonary (91.7%, 95% CI 83.0–96.1), sinonasal (75.0%, 95% CI 63.9–83.6), musculoskeletal (72.2%, 95% CI 61.0–81.2) and gastrointestinal (66.7%, 95% CI 55.2–76.5) involvement predominated. Constitutional symptoms—principally fatigue—were recorded in 97% of patients (95% CI 90.4–99.2) and tracked clinically with disease activity. Cardiac involvement was infrequent (8.3%, 95% CI 3.9–17.0) but uniformly severe. Conclusions: Under systematic symptom probing, constitutional features and pulmonary/sinonasal involvement were recorded more frequently in this single-centre idiopathic HES cohort than in earlier series that pooled HES variants. However, selection bias from a pulmonology and severe-asthma referral pattern, together with differences in symptom ascertainment, likely contributes to these estimates and limits their generalisability to the broader iHES population. Routine echocardiographic screening and structured assessment of fatigue and cognitive symptoms should be incorporated into iHES monitoring.

RationaleAsthma is characterised by inflammation and reversible airway obstruction. However, these features are not always closely related. Fluctuations of daily lung function contain information on asthma phenotypes, exacerbation risk and response to long-acting β-agonists.ObjectivesIn search of subgroups of asthmatic participants with specific lung functional features, we developed and validated a novel clustering approach to asthma phenotyping, which exploits the information contained within the fluctuating behaviour of twice-daily lung function measurements.MethodsForced expiratory volume during the first second (FEV1) and peak expiratory flow (PEF) were prospectively measured over 4 weeks in 696 healthy and asthmatic school children (Protection Against Allergy – Study in Rural Environments (PASTURE)/EFRAIM cohort), and over 1 year in 138 asthmatic adults with mild-to-moderate or severe asthma (Pan-European Longitudinal Assessment of Clinical Course and BIOmarkers in Severe Chronic AIRway Disease (BIOAIR) cohort). Using enrichment analysis, we explored whether the method identifies clinically meaningful, distinct clusters of participants with different lung functional fluctuation patterns.Measurements and main resultsIn the PASTURE/EFRAIM dataset, we found four distinct clusters. Two clusters were enriched in children with well-known clinical characteristics of asthma. In cluster 3, children from a farming environment predominated, whereas cluster 4 mainly consisted of healthy controls. About 79% of cluster 3 carried the asthma-risk allele rs7216389 of the 17q21 locus. In the BIOAIR dataset, we found two distinct clusters clearly discriminating between individuals with mild-to-moderate and severe asthma.ConclusionsOur method identified dynamic functional asthma and healthy phenotypes, partly independent of atopy and inflammation but related to genetic markers on the 17q21 locus. The method can be used for disease phenotyping and possibly endotyping. It may identify participants with specific functional abnormalities, potentially needing a different therapeutic approach.

To collect prospective data from asthma patients treated with medium- (87/5/9µg) or high-strength (172/5/9µg) extrafine single-inhaler beclometasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G, Trimbow ) in a real-world setting. TriMaximize is a non-interventional, prospective, multicenter study conducted in eight European countries (enrollment: 2021-2024). The primary objective was to describe patient characteristics and therapy pathways for adult patients with moderate to severe asthma treated with BDP/FF/G for up to 36 months. Assessments included demographic/clinical characteristics, pulmonary parameters, treatment pathways, asthma control measured by asthma control test (ACT), and health-related quality of life (HrQoL) measured by Mini Asthma Quality of Life Questionnaire (Mini-AQLQ). In total, 1,445 patients (62.8% female; mean age: 57.6 years) were included. Before medium-strength BDP/FF/G initiation, 75.7% of the patients received a fixed ICS/LABA combination. Most patients starting with high-strength BDP/FF/G received fixed ICS/LABA (52.9%) or free ICS/LABA/LAMA (43.2%) combinations as prior therapy. Throughout the study, 87.1% of the patients remained on BDP/FF/G. At month 12, fewer patients (12.4%) used systemic corticosteroids (SCS) compared to baseline (33.2%). Use of rescue medication declined from 6.1 (baseline) to 3.6 puffs/week (month 12). During the first year, 79.5% of the patients experienced neither exacerbations nor used SCS. Three-component clinical remission was achieved in 45.6% (first year) and 59.3% (second/third year) of the patients. Four-component clinical remission was accomplished in 39.5% (first year) and 47.9% (second/third year). Improvements in asthma control (mean ACT change at month 12: 3.9; month 36: 4.8, p<0.0001) and HrQoL (mean Mini-AQLQ change at month 12: 0.8; month 36: 0.9, p<0.0001) exceeded the respective minimal clinically important differences. Forced expiratory volume in 1 second increased by 142 mL after 12 months (p<0.0001). Extrafine, single-inhaler BDP/FF/G therapy was effective and safe in a routine clinical practice setting in a multi-national cohort of patients with moderate to severe asthma.